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1.
ACS Nano ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984372

RESUMEN

Multiscale design of catalyst layers (CLs) is important to advancing hydrogen electrochemical conversion devices toward commercialized deployment, which has nevertheless been greatly hampered by the complex interplay among multiscale CL components, high synthesis cost and vast design space. We lack rational design and optimization techniques that can accurately reflect the nanostructure-performance relationship and cost-effectively search the design space. Here, we fill this gap with a deep generative artificial intelligence (AI) framework, GLIDER, that integrates recent generative AI, data-driven surrogate techniques and collective intelligence to efficiently search the optimal CL nanostructures driven by their electrochemical performance. GLIDER achieves realistic multiscale CL digital generation by leveraging the dimensionality-reduction ability of quantized vector-variational autoencoder. The powerful generative capability of GLIDER allows the efficient search of the optimal design parameters for the Pt-carbon-ionomer nanostructures of CLs. We also demonstrate that GLIDER is transferable to other fuel cell electrode microstructure generation, e.g., fibrous gas diffusion layers and solid oxide fuel cell anode. GLIDER is of potential as a digital tool for the design and optimization of broad electrochemical energy devices.

2.
Int J Cardiol ; 412: 132338, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964551

RESUMEN

BACKGROUND: Surprisingly, despite the high prevalence of metformin use in type 2 diabetes (T2D) patients with heart disease, limited safety data is available regarding metformin use in patients with acute and critical heart disease. METHODS: In this single-center retrospective study, patients admitted to the cardiology department for heart failure (HF) or acute coronary syndrome (ACS) between December 2013 and December 2021 and who underwent arterial blood gas analysis at admission with an estimated glomerular clearance rate of ≥45 ml/min/1.73 m2 were identified. The incidences of hyperlactatemia, acidosis, and 30-day in-hospital mortality were compared between preadmission metformin users and nonusers. RESULTS: Of 526 admissions, 193/193 metformin users/nonusers were selected in a propensity score-matched model. Metformin users had greater lactate levels (2.55 ± 2.07 mmol/l vs. 2.00 ± 1.80 mmol/l P < 0.01), a greater incidence of hyperlactatemia [odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.63-3.98; P < 0.01] and acidosis (OR = 1.78; 95% CI, 1.00-3.16; P < 0.05) at admission and a greater incidence of in-hospital mortality (OR = 3.83; 95% CI, 1.05-13.94; P < 0.05), especially those with HF/acute myocardial infarction, elderly age, or without preadmission insulin use. CONCLUSIONS: Our results suggest that, compared to metformin nonusers, preadmission use of metformin may be associated with a greater incidence of hyperlactatemia and acidosis at admission and greater 30-day in-hospital mortality among T2D patients with HF or ACS at high risk of hypoxia, particularly those without preadmission insulin use. The safety of metformin in this population needs to be confirmed in prospective controlled trials.

3.
J Phys Chem Lett ; 15(27): 7003-7010, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38949564

RESUMEN

A BPAPTPyC organic molecule containing a sandwich structural chromophore is designed and synthesized to produce blue thermally activated delayed fluorescence (TADF). The chromophore is composed of two di(4-tert-butylphenyl)amino donors and one inserted terpyridyl acceptor hitched at positions 1, 8, and 9 of a single carbazole via the p-phenylene group, in which the multiple space π-π interactions between the donor and acceptor enable the molecule to possess the TADF feature with a high energy emission at 470 nm but a low photoluminescence quantum yield (PLQY) and a small proportion of the delayed component. In contrast, the corresponding Zn(BPAPTPyC)Cl2 complex has a high PLQY and a short lifetime with a red-shifted emission due to the enhanced rigidity and electron accepting ability of the terpyridyl group from coordination. A solution-processed organic light-emitting diode (OLED) based on the complex achieves a maximum external quantum efficiency (EQE) of 17.9% with an emission peak at 585 nm, while an OLED of the organic molecule produces blue emission with a maximum EQE of 2.7%.

4.
Nanomedicine (Lond) ; : 1-10, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011932

RESUMEN

Aim: Nano-hydroxyapatite (nHA) is a good nanocarrier to load 223Ra, but the low specific activity (sp.act.) of 223Ra@nHA limits its application in medicine. Methods: We proposed a method for preparing nHA using PEG as a template, which significantly increases the sp.act of 223Ra@nHA and a new method to loaded 99mTc for in vivo tracking. Results: The nHA synthesized using PEG as a template was associated with higher sp.act for 223Ra in comparison to nHA with identical particle size and without PEG. The nHA load 99mTc-MDP was associated with higher labeling rate and stability in comparison to 99mTc. Conclusion: All these findings suggest that using PEG as a template and 99mTc-MDP could be the most effective of synthetic 223Ra/99mTc@nHA.


[Box: see text].

5.
Horm Metab Res ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870985

RESUMEN

This study attempted to build a prostate cancer (PC) prognostic risk model with mitochondrial feature genes. PC-related MTGs were screened for Cox regression analyses, followed by establishing a prognostic model. Model validity was analyzed via survival analysis and receiver operating characteristic (ROC) curves, and model accuracy was validated in the GEO dataset. Combining risk score with clinical factors, the independence of the risk score was verified by using Cox analysis, followed by generating a nomogram. The Gleason score, microsatellite instability (MSI), immune microenvironment, and tumor mutation burden were analyzed in two risk groups. Finally, the prognostic feature genes were verified through a q-PCR test. Ten PC-associated MTGs were screened, and a prognostic model was built. Survival analysis and ROC curves illustrated that the model was a good predictor for the risk of PC. Cox regression analysis revealed that risk score acted as an independent prognostic factor. The Gleason score and MSI in the high-risk group were substantially higher than in the low-risk group. Levels of ESTIMATE Score, Immune Score, Stromal Score, immune cells, immune function, immune checkpoint, and immunopheno score of partial immune checkpoints in the high-risk group were significantly lower than in the low-risk group. Genes with the highest mutation frequencies in the two groups were SPOP, TTN, and TP53. The q-PCR results of the feature genes were consistent with the gene expression results in the database. The 10-gene model based on MTGs could accurately predict the prognosis of PC patients and their responses to immunotherapy.

6.
STAR Protoc ; 5(2): 103099, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38824639

RESUMEN

The MS2-PP7 two-color live-imaging system provides insights into the spatiotemporal dynamics of nascent transcripts at tagged loci. Here, we present a protocol to quantitatively measure the rate of RNA polymerase II elongation for each actively transcribing nucleus in living Drosophila embryos. The elongation rate is calculated by measuring the effective distance and the time elapsed between MS2 and PP7 trajectories. We describe steps for preparing embryo samples, performing live imaging, and measuring the elongation rate. For complete details on the use and execution of this protocol, please refer to Keller et al.1.


Asunto(s)
Embrión no Mamífero , ARN Polimerasa II , Animales , ARN Polimerasa II/metabolismo , ARN Polimerasa II/genética , Embrión no Mamífero/metabolismo , Drosophila/embriología , Drosophila/metabolismo , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética
7.
Chem Sci ; 15(23): 8922-8933, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38873061

RESUMEN

Surface-protecting ligands, as a major component of metal nanoclusters (MNCs), can dominate molecular characteristics, performance behaviors, and biological properties of MNCs, which brings diversity and flexibility to the nanoclusters and largely promotes their applications in optics, electricity, magnetism, catalysis, biology, and other fields. We report herein the design of a new kind of water-soluble luminescent gold nanoclusters (AuNCs) for enzyme-activatable charge transfer (CT) based on the ligand engineering of AuNCs with 6-mercaptopurine ribonucleoside (MPR). This elaborately designed cluster, Au5(MPR)2, can form a stable intramolecular CT state after light excitation, and exhibits long-lived color-tunable phosphorescence. After the cleavage by purine nucleoside phosphorylase (PNP), the CT triplet state can be easily directed to a low-lying energy level, leading to a bathochromic shift of the emission band accompanied by weaker and shorter-lived luminescence. Remarkably, these ligand-engineered AuNCs show high affinity towards PNP as well as decent performance for analyzing and visualizing enzyme activity and related drugs. The work of this paper provides a good example for diversifying physicochemical properties and application scenarios of MNCs by rational ligand engineering, which will facilitate future interest and new strategies to precisely engineer solution-based nanocluster materials.

8.
Drug Des Devel Ther ; 18: 2257-2272, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895176

RESUMEN

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.


Asunto(s)
Autofagia , Medicamentos Herbarios Chinos , MicroARNs , Farmacología en Red , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Psoriasis/patología , Autofagia/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Método Doble Ciego , Adulto , Femenino , Persona de Mediana Edad , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos
9.
Intern Emerg Med ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907757

RESUMEN

Few clinical decision rules have been used to guide clinical management and predict outcomes in patients with pericardial tamponade. The objectives of this study are to identify the echocardiographic features associated with adverse outcomes in patients with pericardial effusions requiring pericardiocentesis and to apply a previously described four-point clinical and echocardiographic score to predict clinical outcomes over 24-hr, 30-day, and 1-year intervals. We performed a retrospective cohort review of patients who had transthoracic echocardiogram (TTE) performed and underwent pericardiocentesis within 48 h of emergency department presentation at two large tertiary care institutions. We constructed different stepwise logistic regression models and examined the associations of TTE characteristics and clinical features with ICU admission, hospital length of stay (h-LOS), and survival. The data set was then employed against a previously proposed scoring system to predict factors associated with clinical outcomes over 24 hr, 30 days, and 1 year. Two hundred thirty-nine patients were included in the final analysis. Echocardiographic characteristics of patients with pericardial tamponade who underwent pericardiocentesis are as follows: 69.1% right ventricular (RV) diastolic collapse, 62.3% exaggerated mitral valve (MV) inflow velocities, 56.4% inferior vena cava (IVC) plethora, and 53.4% right atrial (RA) systolic collapse. Increase in systolic blood pressure and increased variation in MV inflow velocity were associated with reduced ICU admission [OR: 0.94 (CI 0.90, 0.99), 0.28 (CI 0.09, 0.89), respectively]. In addition, a history of malignancy increased the length of hospital stay by about 3.89 days (CI 1.43-6.35, p < 0.01) and prior pericardiocentesis history was associated with 4.82-day increase in hospital stay (CI 1.19-8.45, p = 0.01). In utilizing the previously published prediction score, we found no statistically significant correlation in predicting survival. RV diastolic collapse and exaggerated MV inflow velocity were the most common echocardiographic findings in patients requiring pericardiocentesis. Contrary to prior studies, exaggerated MV inflow velocity was associated with reduced ICU admission. In addition, a previously described prediction score did not correlate with decreased survival in this cohort.

10.
Phys Rev Lett ; 132(23): 230601, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905646

RESUMEN

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

11.
Biomed Mater ; 19(5)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38917812

RESUMEN

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO4/H2O2on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.


Asunto(s)
Antibacterianos , Escherichia coli , Peróxido de Hidrógeno , Indoles , Membranas Artificiales , Metacrilatos , Polímeros , Staphylococcus aureus , Antibacterianos/química , Antibacterianos/farmacología , Polímeros/química , Adsorción , Indoles/química , Indoles/farmacología , Metacrilatos/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/química , Animales , Ensayo de Materiales , Aminoácidos/química , Incrustaciones Biológicas/prevención & control , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Betaína/química , Betaína/análogos & derivados , Adherencias Tisulares/prevención & control
12.
Med Microbiol Immunol ; 213(1): 11, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940844

RESUMEN

BACKGROUND: Obesity-associated male infertility is a common complication of obesity and has been increasing in prevalence. Blautia wexlerae has modulation effects on obesity. However, the action of B. wexlerae on obesity-associated male infertility is unclear. The nod-like receptor protein 3 (NLRP3) inflammasome has become a major target for addressing many diseases, including obesity-associated male infertility. This study aims to investigate the action of B. wexlerae on obesity-associated male infertility and the influence of B. wexlerae on NLRP3 inflammasome. MATERIALS AND METHODS: The fecal samples were collected from 60 infertile men with or without obesity and 30 healthy men. The obesity mice model was established through high-fat diet (HFD) induction. The mating assays evaluated the male infertility of obese mice. A mouse-derived spermatogonia (GC-1 spg) cell viability was detected using the Cell Counting Kit-8 assay. The reactive oxygen species (ROS) were assessed using flow cytometry. Furthermore, immunofluorescence, enzyme-linked immunosorbent assay, and western blotting were applied to measure the gene expressions. RESULTS: Blautia wexlerae was decreased and negatively correlated with interleukin-1 beta (IL-1ß) or IL-18 levels in infertile men with obesity. On the other hand, B. wexlerae improved the mating capability of obese male mice and suppressed oxidative stress and NLRP3 inflammasome via the activation of the acetate receptor. Furthermore, sodium acetate regulated oxidative stress and NLRP3 inflammasome via the activation of the acetate receptor in GC-1 spg cells in vitro. CONCLUSION: The administration of Blautia wexlerae improved obesity-associated male infertility and regulated oxidative stress and NLRP3 inflammasome activities. In general, its administration may be an effective strategy for the treatment of obesity-associated male infertility.


Asunto(s)
Infertilidad Masculina , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Obesidad , Estrés Oxidativo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Animales , Obesidad/complicaciones , Obesidad/metabolismo , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/metabolismo , Inflamasomas/metabolismo , Ratones , Adulto , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Dieta Alta en Grasa , Interleucina-1beta/metabolismo , Ratones Endogámicos C57BL
13.
Environ Sci Technol ; 58(27): 12237-12248, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38934294

RESUMEN

Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing •CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.


Asunto(s)
Titanio , Catálisis , Titanio/química , Oxidación-Reducción , Renio/química , Agua/química , Concentración de Iones de Hidrógeno , Soluciones
14.
Int J Biol Macromol ; 273(Pt 1): 132926, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851610

RESUMEN

In recent years, the development of environmentally friendly packaging materials using biodegradable polymers has emerged as a key challenge for scientists and consumers in response to resource depletion and environmental issues caused by plastic packaging materials. Starch and polyvinyl alcohol (PVA) are being recognized as excellent candidates for producing biodegradable food packaging films. Polymer blending has emerged as a practical approach to overcome the limitations of biopolymer films by developing films with unique properties and enhancing overall performance. This review briefly introduces the molecular structure and properties of starch and PVA, summarizes the common preparation methods and properties of starch/PVA blend films, and focuses on different strategies used to enhance starch/PVA blend films, including nanoparticles, plant extracts, and cross-linking agents. Additionally, this study summarizes the application of starch/PVA blend films as active and smart packaging in food preservation systems. This study demonstrates that starch and PVA blends have potential in manufacturing biodegradable food films with excellent properties due to their excellent compatibility and intermolecular interactions, and can be used as packaging films for a variety of foods to extend their shelf life.


Asunto(s)
Embalaje de Alimentos , Alcohol Polivinílico , Almidón , Alcohol Polivinílico/química , Embalaje de Alimentos/métodos , Almidón/química , Plásticos/química
15.
Opt Express ; 32(8): 14143-14153, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859368

RESUMEN

In this paper, cascaded modal interferometers constructed by strongly-coupled seven-core fiber (SC-SCF) with different lengths are demonstrated for enhanced bending sensing based on Vernier effect. The free spectral range (FSR) of a single SC-SCF interferometer is determined by the length of SC-SCF. Two SC-SCF interferometers with different FSRs are cascaded, in which, one functions as the sensor while the other functions as the reference. The wavelength shift of the envelope of the output spectrum is much larger than that of a single SC-SCF interferometer due to the Vernier effect. Therefore, enhanced sensing can be achieved. Experimental results show that the bending sensitivity of the proposed sensor is improved from -2.20 nm/m-1 (single SC-SCF interferometer) to 42.32 nm/m-1 (cascaded SC-SCF interferometers). The temperature response of the sensor is also investigated. Our proposed cascaded SC-SCF sensor has advantages of high sensitivity, ease of fabrication, and low cost. It is attractive for high precision bending sensing applications.

16.
J Transl Med ; 22(1): 481, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773612

RESUMEN

BACKGROUND: Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated. METHODS: The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays. RESULTS: We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion. CONCLUSION: Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients.


Asunto(s)
Carcinoma de Células Renales , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Neoplasias Renales , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Movimiento Celular/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Ubiquitinación , Estabilidad Proteica , Invasividad Neoplásica , Femenino , Regulación hacia Abajo/genética , Persona de Mediana Edad , Animales
18.
J Biol Chem ; 300(6): 107376, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38762176

RESUMEN

Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl4- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl4-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl4-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of interleukin 6 (IL-6), and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the profibrotic response inspired by Fendrr in the CCl4-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory cross talk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.


Asunto(s)
Hepatocitos , Interleucina-6 , Cirrosis Hepática , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Hepatocitos/metabolismo , Hepatocitos/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Humanos , Ratones , Interleucina-6/metabolismo , Interleucina-6/genética , Masculino , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Factor de Transcripción STAT2/metabolismo , Factor de Transcripción STAT2/genética , Ratones Endogámicos C57BL , Tetracloruro de Carbono/toxicidad
19.
J Clin Anesth ; 96: 111485, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38718685

RESUMEN

STUDY OBJECTIVE: To estimate the incidence of postoperative oxygenation impairment after lung resection in the era of lung-protective management, and to identify perioperative factors associated with that impairment. DESIGN: Registry-based retrospective cohort study. SETTING: Two large academic hospitals in the United States. PATIENTS: 3081 ASA I-IV patients undergoing lung resection. MEASUREMENTS: 79 pre- and intraoperative variables, selected for inclusion based on a causal inference framework. The primary outcome of impaired oxygenation, an early marker of lung injury, was defined as at least one of the following within seven postoperative days: (1) SpO2 < 92%; (2) imputed PaO2/FiO2 < 300 mmHg [(1) or (2) occurring at least twice within 24 h]; (3) intensive oxygen therapy (mechanical ventilation or > 50% oxygen or high-flow oxygen). MAIN RESULTS: Oxygenation was impaired within seven postoperative days in 70.8% of patients (26.6% with PaO2/FiO2 < 200 mmHg or intensive oxygen therapy). In multivariable analysis, each additional cmH2O of intraoperative median driving pressure was associated with a 7% higher risk of impaired oxygenation (OR 1.07; 95%CI 1.04 to 1.10). Higher median intraoperative FiO2 (OR 1.23; 95%CI 1.14 to 1.31 per 0.1) and PEEP (OR 1.12; 95%CI 1.04 to 1.21 per 1 cm H2O) were also associated with increased risk. History of COPD (OR 2.55; 95%CI 1.95 to 3.35) and intraoperative albuterol administration (OR 2.07; 95%CI 1.17 to 3.67) also showed reliable effects. CONCLUSIONS: Impaired postoperative oxygenation is common after lung resection and is associated with potentially modifiable pre- and intraoperative respiratory factors.


Asunto(s)
Terapia por Inhalación de Oxígeno , Neumonectomía , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Incidencia , Factores de Riesgo , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Terapia por Inhalación de Oxígeno/métodos , Sistema de Registros/estadística & datos numéricos , Oxígeno/sangre , Respiración con Presión Positiva/efectos adversos , Respiración con Presión Positiva/métodos , Estados Unidos/epidemiología
20.
Zool Res ; 45(3): 567-574, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38757224

RESUMEN

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes. However, their activity markedly diminishes with payloads exceeding 11 kb. Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs, improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics, metabolic engineering, and transgenic animal production. In this study, we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer ( QBI SP163, ST) and enhanced the nuclear targeting ability using the nuclear localization protein H2B (SHT). The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures (H1299), comparable to the well-established super PiggyBac system. Furthermore, mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads (8 kb, 14 kb, and 24 kb) into zebrafish ( Danio rerio). This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.


Asunto(s)
Elementos Transponibles de ADN , Transgenes , Pez Cebra , Animales , Pez Cebra/genética , Elementos Transponibles de ADN/genética , Humanos , Animales Modificados Genéticamente , Técnicas de Transferencia de Gen
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